Lineage commitment in human stem and lymphoid progenitor populations in bone marrow, umbilical cord blood, mobilized peripheral blood and thymus

 

Our lab studies human hematopoietic stem cells and the process by which they embark on the first stages of lineage commitment. Although the conceptual foundations are very similar between the species, critical biological differences exist between murine and human hematopoiesis, and the tools required to study hematopoietic stem and progenitor cells are necessarily quite different. In particular, studies in human lymphoid commitment have lagged behind those of mouse because of the initial lack of assays for human lymphoid differentiation. Using novel in vitro systems developed by our group, we identified a multi-lymphoid progenitor in umbilical cord blood that gives rise to B, NK, T and dendritic cells (Hao et al, Blood 2001), and also defined the earliest progenitor stages in the human thymus (Hao et al, Blood 2008). A major effort in our lab is now to understand how these processes change during development. Most studies in human hematopoiesis have used umbilical cord blood as it is relatively easy to acquire, leading to a gap in understanding how these processes occur during steady state adult hematopoiesis. In recent studies we identified and performed transcriptome profiling of a progenitor in human adult bone marrow which possesses full lymphoid potential and which likely seeds the human thymus through high L-selectin expression (Kohn et al, Nature Immunology 2012). By studying the progenitor stages in bone marrow from children with different forms of severe combined immune deficiency (SCID), we demonstrated that, unlike murine lymphopoiesis, signaling through the common gamma chain (aka IL2RG) is not required for generation of human lymphoid progenitors or B cell differentiation (Kohn et al, Journal of Immunology 2014). Our current interests include the role of non-coding RNAs in stem and progenitor function.